In spite of the development of antibiotics, pneumoncoccal disease is still the leading cause of death by infectious agents in the United States. Although pneumococcal infections generally respond to treatment with antibiotics in the elderly and in immunodeficient or immunosuppressed patients, the response is often not rapid enough to reverse the disease before fatal damage has been done. We have recently demonstrated that the anti-PC antibodies in the normal serum of mice are protective against type 3 pneumococci. Since the PC antigenic determinant is a component of the cell wall of all strains of pneumococci, anti-PC antibody unlike anti-capsular antibody may be protective against infection with all capsular types. If this is true it might be possible to immunize humans with a potent PC containing immunogen, or treat them with anti-PC hybridoma antibodies. In this study, we propose to determine if mouse and human anti-PC antibody is, in fact, protective against pneumococci with multiple capsular types. We also plan to produce human hybridoma anti-PC and anti-capsular antibodies that may evenually be useful in passive protection of humans from pneumococcal infection. By using a number of hybridoma antibodies of known isotype and idiotype we can determine what effects different heavy chain isotypes and idiotypes have on the protective ability of antibodies. In this way, we may, be able to gain an insight into what advantages there might be in producing the bulk of the IgG anti-carbohydrate antibodies as IgG3 in the mouse and IgG2 in man.